Accurate attenuation correction (AC) on PET/MR is still challenging. The purpose of this study was to evaluate the clinical feasibility of AC based on fast zero-echo-time (ZTE) MRI by comparing it with the default atlas-based AC on a clinical PET/MR scanner. Methods: We recruited 10 patients with malignant diseases not located on the brain. In all patients, a clinically indicated whole-body 18 F-FDG PET/CT scan was acquired. In addition, a head PET/MR scan was obtained voluntarily. For each patient, 2 AC maps were generated from the MR images. One was atlas-AC, derived from T1-weighted liver acquisition with volume acceleration flex images (clinical standard). The other was ZTE-AC, derived from proton-density-weighted ZTE images by applying tissue segmentation and assigning continuous attenuation values to the bone. The AC map generated by PET/CT was used as a silver standard. On the basis of each AC map, PET images were reconstructed from identical raw data on the PET/MR scanner. All PET images were normalized to the SPM5 PET template. After that, these images were qualified visually and quantified in 67 volumes of interest (VOIs; automated anatomic labeling, atlas). Relative differences and absolute relative differences between PET images based on each AC were calculated. 18 F-FDG uptake in all 670 VOIs and generalized merged VOIs were compared using a paired t test. Results: Qualitative analysis shows that ZTE-AC was robust to patient variability. Nevertheless, misclassification of air and bone in mastoid and nasal areas led to the overestimation of PET in the temporal lobe and cerebellum (%diff of ZTE-AC, 2.46% ± 1.19% and 3.31% ± 1.70%, respectively). The j%diffj of all 670 VOIs on ZTE was improved by approximately 25% compared with atlas-AC (ZTE-AC vs. atlas-AC, 1.77% ± 1.41% vs. 2.44% ± 1.63%, P , 0.01). In 2 of 7 generalized VOIs, j%diffj on ZTE-AC was significantly smaller than atlas-AC (ZTE-AC vs. atlas-AC: insula and cingulate, 1.06% ± 0.67% vs. 2.22% ± 1.10%, P , 0.01; central structure, 1.03% ± 0.99% vs. 2.54% ± 1.20%, P , 0.05). Conclusion: The ZTE-AC could provide more accurate AC than clinical atlas-AC by improving the estimation of head-skull attenuation. The misclassification in mastoid and nasal areas must be addressed to prevent the overestimation of PET in regions near the skull base.